MicroRNA expression profile and network in colorectal carcinoma after chemotherapy

Colorectal cancer (CRC) is the third cause of cancer-related death in western societies. Currently, the most common pharmacologic approach to CRC treatment is based on blocking the EGFR pathway through monoclonal antibodies against EGFR (i.e. Cetuximab or Panitumumab). In recent years, the microRNA global gene expression approach has been exploited to identify CRC specific miRNA signatures and to discover new diagnostic and prognostic markers. However, the relationship between the response to chemotherapy in CRC and miRNA expression remains unknown. We investigated the miRNA involvement in CRC drug response by profiling, through Real-Time TaqMan PCR, the expression of 677 microRNAs in human CRC cell lines sensitive or resistant to cetuximab (CaCo2 and HCT116, respectively), at 24 hours and 48 hours after treatment (PT). CaCo2 and HCT116 expressed different sets of miRNAs, both at steady state as at 24 hours and 48 hours PT: specifically, at 24 hours PT in CaCo2 22 miRNAs (3%) were differentially expressed respect to matched controls, and 12 (1.7%) at 48 hours PT; in HCT116, 18 miRNAs (2.6%) were differentially expressed at 24 hours PT, and 17 (2.5%) 48 hours PT. The fold change ranged from 5 to 1000. Intriguingly, the miRNA profile of the two cell lines displayed about a 15.6% discrepancy, both at 24 hours and at 48 hours PT. Among the targets of these miRNAs, we detected a high occurrence of GO categories such as cell proliferation, apoptosis, and transcription regulation. We suggest that the different miRNA profile of CaCo2 and HCT116 may appropriately explain their antithetical response to cetuximab. The identification of miRNAs, whose expression is linked the efficacy of chemotherapy, should eventually allow to check in a noninvasive manner the response of patients to treatment and possibly leads to a better understanding of the molecular mechanisms of drug response.